A simple self-reported adherence tool as a predictor of viral rebound in people with viral suppression on antiretroviral therapy.

OBJECTIVES: The aim of the study was to investigate the relationship between self-reported antiretroviral therapy (ART) adherence and virological outcomes in the multinational Strategies for Management of Antiretroviral Therapy (SMART) study. METHODS: Eligible participants were from the continuous ART arm and had at least one viral load (VL) ≤ 50 HIV-1 RNA copies/mL and a subsequent VL value (VL pair). Self-reported adherence was measured at each visit using a five-point Likert scale which employed a 7-day recall. High adherence was defined as taking 'all pills every day' (level 1) for every regimen component; all others had suboptimal adherence (levels 2 - 5). In individuals with VL suppression (≤ 50 copies/mL), the association between adherence (at the time of VL suppression) and VL rebound (> 200 copies/mL at next visit) was assessed using multivariable logistic regression with generalized estimating equations. RESULTS: A total of 10 761 sets of VL pairs from 1986 participants were included in the study. For 1220 (11%) VL pairs, adherence was suboptimal. For 507 VL pairs (5%), VL rebound occurred. The risk of rebound generally increased as adherence decreased: 4.2% for level 1, 7.7% for level 2, 16.3% for level 3, 9.4% for level 4 and 12.9% for level 5. In multivariable analysis, suboptimal adherence at the time of suppression was associated with a 50% increased odds of experiencing subsequent VL rebound [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.19-1.92; P = 0.0023], compared with high adherence. CONCLUSIONS: Self-reported suboptimal adherence in people with VL suppression is associated with an increased risk of VL rebound. Our findings highlight the importance of continued adherence counselling, even in people with VL suppression, and to ensure that people with HIV infection maintain excellent adherence in order to minimize the risk of VL rebound.

The CASE adherence index: A novel method for measuring adherence to antiretroviral therapy.

The Center for Adherence Support Evaluation (CASE) Adherence Index, a simple composite measure of self-reported antiretroviral therapy (ART) adherence, was compared to a standard three-day self-reported adherence measure among participants in a longitudinal, prospective cross-site evaluation of 12 adherence programs throughout the United States. The CASE Adherence Index, consisting of three unique adherence questions developed for the cross-site study, along with a three-day adherence self-report were administered by interviews every three months over a one-year period. Data from the three cross-site adherence questions (individually and in combination) were compared to three -day self-report data and HIV RNA and CD4 outcomes in cross-sectional analyses. The CASE Adherence Index correlated strongly with the three-day self-reported adherence data (p < 0.001) and was more strongly associated with HIV outcomes, including a 1-log decline in HIV RNA level (maximum OR = 2.34; p < 0.05), HIV RNA < 400 copies/ml (maximum OR = 2.33; p < 0.05) and performed as well as the three-day self-report when predicting CD4 count status. Participants with a CASE Index score >10 achieved a 98 cell mean increase in CD4 count over 12 months, compared to a 41 cell increase for those with scores < or =10 (p < 0.05). The CASE Adherence Index is an easy to administer instrument that provides an alternative method for assessing ART adherence in clinical settings.

Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence.

This study assesses changes in quality of life (QoL) over time among HIV-infected individuals receiving antiretroviral therapy (ART) and evaluates how this relates to ARTadherence. Prospective, longitudinal data were examined from 1050 participants in two large, randomized, multi-centre antiretroviral clinical trials. QoL was assessed by the SF-12; adherence by the Terry Beirn Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-report. Participants included 20% women, 53% African Americans, 16% Latinos; mean age was 39 years; mean baseline CD4+ cell count 230 cells/mm3; 89% were ART-naïve at entry. Baseline physical and mental health summary QoL scores were 45.4 and 42.9, comparable to scores reported in other advanced HIV populations. Significant improvements in mean QoL scores were seen for the group as a whole after 1 to 4 months on new ART regimens, and persisted for 12 months. Participants reporting 100% ART adherence achieved significantly higher QoL scores at 12 months compared to those with poorer adherence, particularly if 100% adherence was consistent (p < 0.001). Those with at least 80% ART adherence had smaller gains in QoL at 12 months when compared to baseline, while those with < 80% adherence had worsening of QoL. In this analysis, ART adherence was associated with improved QoL, particularly if adherence was sustained.

A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To determine the short-term effects of using genotypic antiretroviral resistance testing (GART) with expert advice in the management of patients failing on a protease inhibitor and two nucleoside reverse transcriptase inhibitors. DESIGN: Prospective randomized controlled trial. SETTING: Multicenter community-based clinical trials network. PATIENTS: One-hundred and fifty-three HIV-infected adults with a threefold or greater rise in plasma HIV-1 RNA on at least 16 weeks of combination antiretroviral therapy. INTERVENTIONS: Randomization was either to a GART group, where genotype interpretation and suggested regimens were provided to clinicians, or to a no-GART group, where treatment choices were made without such input. MAIN OUTCOMES MEASURES: Plasma HIV-1 RNA levels and CD4 cell counts were measured at 4, 8, and 12 weeks following randomization. The primary endpoint was change in HIV-1 RNA levels from baseline to the average of the 4 and 8 week levels. RESULTS: The average baseline CD4 cell count was 230 x 10(6) cells/l and the median HIV-1 RNA was 28,085 copies/ml. At entry, 82 patients were failing on regimens containing indinavir, 51 on nelfinavir, 11 on ritonavir, and nine on saquinavir. HIV-1 RNA, averaged at 4 and 8 weeks, decreased by 1.19 log10 for the 78 GART patients and -0.61 log10 for the 75 no-GART patients (treatment difference: -0.53 log, 95% confidence interval, -0.77 to -0.29; P = 0.00001). Overall, the best virologic responses occurred in patients who received three or more drugs to which their HIV-1 appeared to be susceptible. CONCLUSION: In patients failing triple drug therapy, GART with expert advice was superior to no-GART as measured by short-term viral load responses.

Discontinuation of prophylaxis against Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy. METHODS: We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia. RESULTS: A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of confirmed M. avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years). Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002). CONCLUSIONS: Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy.

Risk factors and outcome of human immunodeficiency virus-infected patients with sporadic multidrug-resistant tuberculosis in New York City.

SETTING: An 880 bed university teaching hospital in New York City. OBJECTIVE: To assess risk factors and outcome for sporadic cases of multidrug-resistant tuberculosis (MDR-TB) in persons with human immunodeficiency virus (HIV) infection. DESIGN: In a retrospective cohort analysis, 13 HIV-positive patients with MDR-TB (cases) diagnosed between January 1991 and December 1993 were compared to 31 HIV-infected patients with susceptible or single drug-resistant tuberculosis (controls) diagnosed during the same time period to assess for differences in risk factors and outcome. RESULTS: Risk factors for MDR-TB included homosexual contact as a risk for HIV transmission, prior antiretroviral therapy and Pneumocystis carinii prophylaxis. Fatality rates were 62% for MDR-TB patients and 26% for controls (P < 0.04). The median survival time was 5.8 months for cases and 9.8 months for controls. Risk factors associated with death included multidrug-resistance and CD4-lymphocyte counts below 200. CONCLUSION: Sporadic MDR-TB infection in HIV-infected patients is associated with increased morbidity and mortality compared to infection with susceptible or single-drug-resistant TB. The median survival for HIV-infected patients with MDR-TB in this study is, however, two to three times longer than previously reported in MDR-TB outbreaks.

Association of penicillin-resistant pneumococci with residence in a pediatric chronic care facility.

Risk factors for the acquisition of penicillin-resistant pneumococci (PRP) were analyzed at a university hospital in New York City. Patients with PRP and control patients with penicillin-sensitive pneumococcal infections were compared. In 1994, 24 (21%) of 113 patients with Streptococcus pneumoniae infections had PRP; 13 PRP isolates were from children and 11 from adults. Only white race (P < .05) and residence in a pediatric chronic care facility (P < .05) were significantly associated with penicillin resistance. An investigation at one chronic care facility revealed that 33% of children (17/52) had PRP colonization. Fourteen of the 17 PRP isolates were also resistant to ceftriaxone. Prior antibiotic use and specifically beta-lactam use were associated with penicillin resistance. All typeable PRP isolates were multidrug-resistant serotype 23. Pediatric residents in chronic care facilities may be an important reservoir of PRP and may serve as a source of PRP transmission when they are transferred to acute care hospitals.

Induction of macrophage antiprotozoal activity by monocyte chemotactic and activating factor.

To determine if monocyte chemotactic and activating factor (MCAF) induces intracellular antimicrobial activity, human monocyte-derived macrophages were treated with MCAF and challenged with Toxoplasma gondii and Leishmania donovani. Pretreatment with MCAF induced macrophages to inhibit protozoal replication by approximately 50%. These findings suggest a potential host defense role for MCAF in the inflammatory response to intracellular pathogens.